While many infectious diseases have been controlled or eliminated by medical science, chronic diseases--such as heart attack, stroke and cancer--have emerged as major causes of death. Where death does not result from stroke, the victim is often seriously disabled. The death rate for stroke victims is over 2 per 1,000 in the United States. The Japanese, while having one of the lowest incidences of death from heart disease, have one of the highest from strokes.
Various different compounds have been suggested as useful for the treatment of stroke. For example, it appears that aspirin may reduce the risk of transient ischemic attacks, or small strokes, and deaths from stroke. U.S. Pat. No. 4,256,883, inventors Nicolaou et al., issued Mar. 17, 1981, discloses prostacyclin analogs said to be useful in vascular constrictions and in cerebral strokes associated with essential hypertension. U.S. Pat. No. 4,364,951, inventors Skuballa et al., issued Dec. 21, 1982, discloses prostacyclins said to possess properties useful, inter alia, in treating stroke. U.S. Pat. No. 4,394,385, inventor Cragoe, issued July 19, 1983, discloses the use of benzofuranyloxyacetic acids and anti-inflammatory steroids said to be useful in controlling edema from ischemic stroke.
It has been recently reported that the opiate antagonist naloxone can reverse neurologic deficits secondary to cerebral ischemia, whereas morphine exacerbates them. Baskin and Hosobuchi, "Naloxone reversal of ischaemic neurological deficits in man," Lancet 2:272-275 (1981). It has also been reported that neurologic deficits produced by unilateral carotid ligation in gerbils can be reversed by the intraperitoneal administration of naloxone. Hosobuchi et al., "Reversal of induced ischemic neurologic deficit in gerbils by the opiate antagonist naloxone," Science 215:69-71 (1982).
However, Levy, et al. have reported that treatment with naloxone did not produce improved neurologic function or alter infarct size in gerbils that had undergone temporary carotid occlusion. ("Failure of naloxone to limit clinical or morphological brain damage in gerbils with unilateral carotid artery occlusion," Abstracts of the 12th Annual Meeting of the Society for Neuroscience, p. 248 (1982).) Similarly, Holaday and D'Amato reported that naloxone had no beneficial effect on either survival or neurologic function in several different models of stroke in gerbils. ("Naloxone or TRH fails to improve neurologic deficits in gerbil models of `stroke`," Life Science 31:385-392 (1982).)